The object of the proposed research is to understand the roles of cadherins in hippocampal synaptogenesis. Both genetic and biochemical techniques will be used; Cadherin function will be perturbed in cultured neurons using dominant-negative constructs, and then in mouse embryos using genetic techniques. The effects of the perturbations on synaptic structure, organization and function will be examined. Secondly, we will screen for regulators of cadherin function using conventional and novel yeast-two hybrid screens. This work will shed light on the mystery of how synapses are formed and organized, and on how synapses are modulated in processes such as learning, memory, aging and diseases.